Episodic ataxia, type 9

Summary

Episodic ataxia, type 9 (MONDO:0030064) is a disease caused by SCN2A (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SCN2A (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 81

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	episodic ataxia, type 9
Mondo ID	MONDO:0030064
OMIM	618924
DOID	DOID:0060965
UMLS	C5394520
MedGen	1714171
GARD	0025520
Is cancer (heuristic)	no

Also known as: EA9 · EPISODIC ATAXIA, TYPE 9 · episodic ataxia, type 9

Data availability: 81 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › atactic disorder › hereditary ataxia › hereditary episodic ataxia › episodic ataxia, type 9

Related subtypes (8): episodic ataxia type 2, episodic ataxia type 1, episodic ataxia type 4, episodic ataxia type 3, episodic ataxia type 7, episodic ataxia type 6, episodic ataxia type 5, episodic ataxia type 8

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

81 retrieved; paginated sample, class counts are floors:

24 uncertain significance, 14 conflicting classifications of pathogenicity, 13 pathogenic, 11 likely pathogenic, 7 benign, 6 pathogenic/likely pathogenic, 6 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
2627658	NM_001040142.2(SCN2A):c.[4565G>C;5644C>G]		Pathogenic	no assertion criteria provided
12878	NM_001040142.2(SCN2A):c.2674G>A (p.Val892Ile)	SCN2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1704269	NM_001040142.2(SCN2A):c.4789T>C (p.Phe1597Leu)	SCN2A	Pathogenic	no assertion criteria provided
207028	NM_001040142.2(SCN2A):c.5644C>G (p.Arg1882Gly)	SCN2A	Pathogenic	criteria provided, multiple submitters, no conflicts
29885	NM_001040142.2(SCN2A):c.304C>T (p.Arg102Ter)	SCN2A	Pathogenic	criteria provided, multiple submitters, no conflicts
29886	NM_001040142.2(SCN2A):c.3631G>A (p.Glu1211Lys)	SCN2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
29888	NM_001040142.2(SCN2A):c.788C>T (p.Ala263Val)	SCN2A	Pathogenic	criteria provided, multiple submitters, no conflicts
3366956	NM_001040142.2(SCN2A):c.605+1G>C	SCN2A	Pathogenic	criteria provided, single submitter
3370511	NM_001040142.2(SCN2A):c.1267G>A (p.Val423Met)	SCN2A	Pathogenic	criteria provided, single submitter
3382990	NM_001040142.2(SCN2A):c.4385del (p.Phe1462fs)	SCN2A	Pathogenic	criteria provided, single submitter
378927	NM_001040142.2(SCN2A):c.781G>A (p.Val261Met)	SCN2A	Pathogenic	criteria provided, multiple submitters, no conflicts
379254	NM_001040142.2(SCN2A):c.3956G>T (p.Arg1319Leu)	SCN2A	Pathogenic	criteria provided, multiple submitters, no conflicts
410982	NM_001040142.2(SCN2A):c.3955C>T (p.Arg1319Trp)	SCN2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
432034	NM_001040142.2(SCN2A):c.2810G>A (p.Arg937His)	SCN2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
493288	NM_001040142.2(SCN2A):c.2548C>T (p.Arg850Ter)	SCN2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
870747	NM_001040142.2(SCN2A):c.4949T>C (p.Leu1650Pro)	SCN2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
932954	NM_001040142.2(SCN2A):c.4901G>A (p.Gly1634Asp)	SCN2A	Pathogenic	no assertion criteria provided
946767	NM_001040142.2(SCN2A):c.843G>A (p.Trp281Ter)	SCN2A	Pathogenic	criteria provided, multiple submitters, no conflicts
984895	NM_001040142.2(SCN2A):c.1819C>T (p.Arg607Ter)	SCN2A	Pathogenic	criteria provided, multiple submitters, no conflicts
1704268	NM_001040142.2(SCN2A):c.781_782delinsTC (p.Val261Ser)	SCN2A	Likely pathogenic	no assertion criteria provided
2572541	NM_001040142.2(SCN2A):c.477-2A>G	SCN2A	Likely pathogenic	criteria provided, single submitter
3024239	NM_001040142.2(SCN2A):c.4309-2A>G	SCN2A	Likely pathogenic	criteria provided, single submitter
3065413	NM_001040142.2(SCN2A):c.4952T>G (p.Phe1651Cys)	SCN2A	Likely pathogenic	criteria provided, single submitter
3238770	NM_001040142.2(SCN2A):c.4481A>G (p.Gln1494Arg)	SCN2A	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3382361	NM_001040142.2(SCN2A):c.5616G>A (p.Met1872Ile)	SCN2A	Likely pathogenic	criteria provided, single submitter
801777	NM_001040142.2(SCN2A):c.1384-2A>G	SCN2A	Likely pathogenic	criteria provided, multiple submitters, no conflicts
976279	NM_001040142.2(SCN2A):c.620T>C (p.Phe207Ser)	SCN2A	Likely pathogenic	criteria provided, multiple submitters, no conflicts
984815	NM_001040142.2(SCN2A):c.593T>A (p.Val198Asp)	SCN2A	Likely pathogenic	no assertion criteria provided
988710	NM_001040142.2(SCN2A):c.4822+1G>A	SCN2A	Likely pathogenic	no assertion criteria provided
988714	NM_001040142.2(SCN2A):c.1912del (p.Leu638fs)	SCN2A	Likely pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 16 · Orphanet: 8 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
SCN2A	Strong	Autosomal dominant	episodic ataxia, type 9	16

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SCN2A	Orphanet:140927	Self-limited neonatal-infantile epilepsy
SCN2A	Orphanet:1934	Early infantile developmental and epileptic encephalopathy
SCN2A	Orphanet:2131	Alternating hemiplegia of childhood
SCN2A	Orphanet:293181	Epilepsy of infancy with migrating focal seizures
SCN2A	Orphanet:306	Self-limited infantile epilepsy
SCN2A	Orphanet:33069	Dravet syndrome
SCN2A	Orphanet:36387	Genetic epilepsy with febrile seizure plus
SCN2A	Orphanet:697160	Infantile epileptic spasms syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SCN2A	HGNC:10588	ENSG00000136531	Q99250	Sodium channel protein type 2 subunit alpha	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SCN2A	Sodium channel protein type 2 subunit alpha	Mediates the voltage-dependent sodium ion permeability of excitable membranes.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Ion channel	1	111.5×	0.009

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SCN2A	Ion channel	yes		IQ_motif_EF-hand-BS, Na_channel_asu, Ion_trans_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
Brodmann (1909) area 23	1
cerebellar vermis	1
middle temporal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCN2A	187	broad	marker	middle temporal gyrus, Brodmann (1909) area 23, cerebellar vermis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SCN2A	2,810

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SCN2A	Q99250	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Interaction between L1 and Ankyrins	1	368.4×	0.010	SCN2A
Phase 0 - rapid depolarisation	1	346.1×	0.010	SCN2A
Sensory perception of taste	1	335.9×	0.010	SCN2A
Sensory perception of sweet, bitter, and umami (glutamate) taste	1	278.5×	0.010	SCN2A
L1CAM interactions	1	120.2×	0.017	SCN2A
Cardiac conduction	1	108.8×	0.017	SCN2A
Sensory Perception	1	95.2×	0.017	SCN2A
Muscle contraction	1	77.2×	0.018	SCN2A
Axon guidance	1	45.1×	0.026	SCN2A
Nervous system development	1	42.9×	0.026	SCN2A
Developmental Biology	1	14.5×	0.069	SCN2A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
intrinsic apoptotic signaling pathway in response to osmotic stress	1	8426.0×	0.001	SCN2A
cardiac muscle cell action potential involved in contraction	1	702.2×	0.007	SCN2A
neuronal action potential	1	481.5×	0.007	SCN2A
sodium ion transport	1	271.8×	0.007	SCN2A
myelination	1	251.5×	0.007	SCN2A
sodium ion transmembrane transport	1	203.0×	0.007	SCN2A
neuron apoptotic process	1	185.2×	0.007	SCN2A
memory	1	183.2×	0.007	SCN2A
cellular response to hypoxia	1	121.2×	0.009	SCN2A
nervous system development	1	45.9×	0.022	SCN2A

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
SCN2A	BEPRIDIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN2A	99	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BEPRIDIL	4	SCN2A
DIBUCAINE	4	SCN2A
ARTICAINE	4	SCN2A
BUPIVACAINE	4	SCN2A
IMIPRAMINE	4	SCN2A
DROPERIDOL	4	SCN2A
DICYCLOMINE	4	SCN2A
TETRABENAZINE	4	SCN2A
PHENIRAMINE	4	SCN2A
PRILOCAINE	4	SCN2A
PROPOXYCAINE	4	SCN2A
PROPARACAINE	4	SCN2A
HEXYLCAINE	4	SCN2A
PRAMOXINE	4	SCN2A
BENOXINATE	4	SCN2A
QUINIDINE	4	SCN2A
FELODIPINE	4	SCN2A
PHENYTOIN	4	SCN2A
QUININE	4	SCN2A
NISOLDIPINE	4	SCN2A
NIFEDIPINE	4	SCN2A
PRAZOSIN	4	SCN2A
DILTIAZEM	4	SCN2A
PRENYLAMINE	4	SCN2A
COCAINE	4	SCN2A
TRIFLUOPERAZINE	4	SCN2A
CINNARIZINE	4	SCN2A
THIORIDAZINE	4	SCN2A
ETIDOCAINE	4	SCN2A
CHLORPHENIRAMINE	4	SCN2A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
SCN2A	203	Binding:172, Functional:20, ADMET:10, Toxicity:1

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
SCN2A	203

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
BEPRIDIL	4	SCN2A
DIBUCAINE	4	SCN2A
ARTICAINE	4	SCN2A
BUPIVACAINE	4	SCN2A
IMIPRAMINE	4	SCN2A
DROPERIDOL	4	SCN2A
DICYCLOMINE	4	SCN2A
TETRABENAZINE	4	SCN2A
PHENIRAMINE	4	SCN2A
PRILOCAINE	4	SCN2A
PROPOXYCAINE	4	SCN2A
PROPARACAINE	4	SCN2A
HEXYLCAINE	4	SCN2A
PRAMOXINE	4	SCN2A
BENOXINATE	4	SCN2A
QUINIDINE	4	SCN2A
FELODIPINE	4	SCN2A
PHENYTOIN	4	SCN2A
QUININE	4	SCN2A
NISOLDIPINE	4	SCN2A
NIFEDIPINE	4	SCN2A
PRAZOSIN	4	SCN2A
DILTIAZEM	4	SCN2A
PRENYLAMINE	4	SCN2A
COCAINE	4	SCN2A
TRIFLUOPERAZINE	4	SCN2A
CINNARIZINE	4	SCN2A
THIORIDAZINE	4	SCN2A
ETIDOCAINE	4	SCN2A
CHLORPHENIRAMINE	4	SCN2A

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SCN2A
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.